The goal of this Mentored Research Scientist Development Award is to support the Principal Investigator to gain the research knowledge, skills and experience to conduct environmental, gerontological and genetic epidemiology studies. This award will promote the candidate's ability to achieve the long-term goal of developing into an independent investigator. The proposed career development plan aims to build on the candidate's prior research experience in environmental epidemiology with new training in genetics, epidemiology of aging, and neurotoxicology. The scientific goals of this project are to understand how long term environmental exposures to lead and air pollution affect age-related pathological changes, namely, depressed cardiac function, and two novel outcomes that have been relatively little studied in environmental health, age-related cataract and hearing loss. In addition, the project aims to identify factors that impact susceptibility to such pollutants in an aging population. These health endpoints are leading chronic health conditions experienced by the older adults, but the biological mechanisms by which pollution exposures may impact these age-related conditions are poorly understood. The candidate will not only examine independent effects of lead and traffic-related particles, but focus on genes involved in the pathway of iron regulation metabolism which may modify the lead and particle responses. The investigator will also examine if the associations between pollutants and age-related diseases are modified by dietary intake of antioxidants (vitamins C and E, carotenoids, and cruciferous vegetables) and omega-3 fatty acids. In order to apply the candidate's past research background in these research aims in the field of gene-environment interaction and epidemiology of aging, additional training and mentorship is necessary. The proposed career development plan includes working with established experts in metals and air pollution epidemiology, genetic epidemiology, gerontological epidemiology, neurotoxicology, ophthalmology and otolaryngology, and is enhanced by didactic coursework, laboratory training and attendance in seminars and national/international meetings. This proposal will take advantage of the data and archived samples from a large, well-phenotyped, on-going, longitudinal cohort of community-residing elderly men, the Normative Aging Study, and for some of the specific aims, a sub-sample of the Nurses' Health Study will be utilized. Relevance: As the aging population grows, the need to better understand the causes of age-related pathological changes is required, but little is known about the impacts of environmental pollutants on such age-related diseases. This project will identify which sub-population in terms of genetic polymorphisms and nutrient intakes is more susceptible to environmental exposures to lead and air pollution, and ultimately suggest preventive public health strategies to improve the quality of life in the aging population.